Artificial renal tubule can be used in renal substitution therapy. For example, bioartificial renal tubule assist devices (RAD) have been developed and tested, which utilizes hemodialysis hollow fiber membranes. Generally, these fiber membranes are suitable for hemofiltration or hemodialysis.
An asymmetrical microporous hollow fiber for hemodialysis is described in U.S. Pat. No. 4,906,375 to Heilmann, issued Mar. 6, 1990 (referred to herein as “Heilmann”). The fiber has an inner barrier layer and an outer foam-like supporting structure, and is formed of a hydrophobic organic polymer. The hydrophobic organic polymer may be polysulfones such as polyethersulfones (PES). The outer supporting structure is a supporting membrane with a substantially larger pore size than that of the inner barrier layer. The fiber is formed using a spinning system as described in U.S. Pat. No. 3,691,068 to Cross, issued Sep. 12, 1972 (referred to herein as “Cross”). In particular, a casting solution is introduced into a nozzle or spinneret with a precipitating liquor. The casting solution contains the hydrophobic organic polymer, a hydrophilic polymer such as polyvinyl pyrrolidone (PVP), and an aprotic solvent such as N-methylpyrrolidone (NMP). The precipitating liquor may contain NMP and a non-solvent such as water. The casting solution and the precipitating liquor are passed through the spinneret simultaneously and the extruded fiber is precipitated from the inside to the outside. The extruded fiber is passed into a washing bath, where the upper surface of the washing bath is separated from the spinneret by an air gap. The air gap is provided so that full precipitation of components has occurred before the precipitated polymer solution enters the washing bath. The spinning process described in Heilmann and Cross is known in the art as dry-wet spinning, or gel spinning.
US 2009/0209019 to Saito et al., published Aug. 20, 2009 (referred to herein as “Saito”), discloses a bioartificial renal tubule suitable for continuous hemofiltration. The bioartificial renal tubule includes an artificial membrane having an inner surface coated with renal tubular epithelial cells. The hollow fiber membrane has uniformly distributed micropores, and may include polysulfone, polyethersulfoner, polyacrylonitrile, polyvinyl alcohol, and cellulose acetate. An extracellular matrix may be attached to the hollow fiber, which includes collagen I, collagen IV, laminin, fibronectin, and Pronectin.
EP 1634610 to Mabuchi et al., published Mar. 15, 2006 (referred to herein as “Mabuchi”), discloses a polysulfone-based hollow fiber membrane with selective permeability. Mabuchi teaches that the average open pore area on the outer surface of the hollow fiber membrane is preferably 0.3 to 1.0 μm2. Mabuchi discloses that fiber membranes are formed by simultaneously extruding a membrane-forming solution and an interior-coagulation solution, through a nozzle, passing the extruded solution through an air gap, and then coagulating the solution in an aqueous solution.
In the development of artificial renal tubule devices reported in the literature, it is typical to seed cells in hollow fiber membranes as follows. The lumen surface of the hollow fiber is first coated with an extracellular matrix (ECM), and a cell-suspended solution is next introduced into the fiber lumen. After an extended period (typically hours), the cells will settle down under gravity and attach to the ECM-coated bottom surface. The fiber needs to be rotated after a seeding period, e.g. by 90 degrees, to seed another side of the lumen surface. In this technique, four seeding periods are typically required to seed cells on all sides of the lumen surface.